What corrective action would you take if a result on the instrument exceeds the upper linearity limit (Analytical Measurement Range - AMR)?

Corrective Actions for Results Exceeding Upper Linearity Limit (AMR)

When a test result exceeds the upper linearity limit (analytical measurement range), the sample must be diluted with an appropriate diluent and retested to obtain an accurate result within the validated linear range of the instrument.

Understanding Linearity and AMR

The Analytical Measurement Range (AMR) represents the range of analyte concentrations over which an instrument has been validated to measure with acceptable accuracy, precision, and linearity. When results exceed this range:

• Signal response often becomes sublinear at high concentrations 1
• Detector saturation can occur, which blunts signals for abundant compounds 1
• Ion trap instruments may experience space-charge effects leading to signal decreases 1

Step-by-Step Corrective Action Protocol

1. Identify the exceedance: Confirm that the result truly exceeds the established upper linearity limit (AMR) for the specific analyte

2. Document the initial result: Record that the initial result exceeded the upper linearity limit in the laboratory information system

3. Perform appropriate dilution:

   • Select a suitable diluent compatible with the test methodology
   • Calculate an appropriate dilution factor based on the estimated concentration
   • Prepare the dilution using calibrated pipettes and proper technique

4. Retest the diluted sample:

   • Analyze the diluted sample using the same method
   • Ensure the result of the diluted sample falls within the validated linear range

5. Calculate the final result:

   • Multiply the result of the diluted sample by the dilution factor
   • Document both the dilution factor and the calculation performed

6. Verify results:

   • For critical values or unexpected results, consider preparing a second dilution at a different ratio to confirm accuracy
   • For discordant results between different dilutions, prepare a third dilution 2

Documentation Requirements

• Record the original result that exceeded the AMR
• Document the dilution factor used
• Record the result of the diluted sample
• Document the calculated final result
• Note any additional verification steps taken

Special Considerations

For Metabolite Measurements

• Be aware that LC-MS systems can be subject to detector saturation at high concentrations 1
• Ion suppression can occur with high-abundance ions, affecting quantitation 1
• Consider sample cleanup methods for complex samples to minimize ion suppression 1

For Clinical Laboratory Testing

• For diagnostic tests like glucose or A1C, accurate quantitation is critical as these directly impact patient diagnosis and management 1
• The College of American Pathologists (CAP) requires periodic verification of the analytical measurement range of quantitative test systems 3

Quality Control Measures

• Periodically verify the linear range, analytical measurement range, and lower limit of quantification for all quantified compounds 1
• Establish protocols for addressing values that fall outside performance limits 1

Common Pitfalls to Avoid

• Reporting results above the AMR without dilution: This leads to inaccurate results due to nonlinearity at high concentrations
• Using inappropriate dilution factors: Too small dilutions may still yield results above AMR; too large dilutions may introduce unnecessary error
• Failing to document dilution procedures: All dilution steps must be clearly documented for reproducibility
• Neglecting to verify critical results: High-impact results should be confirmed with additional testing
• Overloading analytical systems: This compromises quantitative performance and should be avoided 1

By following this systematic approach to handling results that exceed the upper linearity limit, laboratories can ensure accurate and reliable test results that directly impact patient diagnosis, treatment decisions, and outcomes.